The synthesis of extractant hosts such as the macrocyclic crown ethers (including their nitrogen and sulfur substituted analogs), porphyrins, cryptands, calixarenes, and the like, frequently afford mixtures of the desired (predetermined) macrocyclic extractant molecule and acyclic starting materials and/or partial reaction products. In addition to the presence of these synthesis reaction byproducts, different stereochemical conformations of the predetermined macrocyclic extractant can also be present (e.g., the cone, partial cone, 1,2-alternate, and 1,3-alternate conformations of calix[4]arene), and purification is frequently required to isolate the most desirable stereoisomer(s) for a given application.
The crown ether 4,4′(5′)-di-t-butylcyclohexano-18-crown-6 (DtBuCH18C6, FIG. 1) is illustrative of a highly selective extractant for the removal of Sr2+ and Pb2+ from acidic solutions that has been used over the past ten years in solvent extraction-based separations for the removal of the highly radioactive 90Sr fission product from acidic nuclear wastes [Horwitz et al., Solvent Extr. Ion Exch. (1990), 8, 557–572; Horwitz et al., Solvent Extr. Ion Exch. (1991), 9, 1–25; Horwitz et al., U.S. Pat. No. 5,100,585 (1992); Horwitz et al., U.S. Pat. No. 5,344,623 (1994); Law et al., INEEL/EXT-97-00832; Idaho National Engineering Laboratory; Idaho Falls, Id., 1997; Wood et al., INEEL/CON—97-01431; Idaho National Environmental and Engineering Laboratory; Idaho Falls, Id., 1998; and Horwitz et al., In Metal-Ion Separation and Preconcentration: Progress and Opportunities; Bond et al. Eds.; American Chemical Society: Washington, D.C., 1999; Vol. 716, pages 20–50] and in extraction chromatographic resin-based separations for Sr2+ [Horwitz et al., Anal. Chem. (1991), 63:522–525; Horwitz et al., Solvent Extr. Ion Exch. (1992), 10:313–336; Horwitz et al., U.S. Pat. No. 5,110,474, (1992); Horwitz et al., U.S. Pat. No. 5,346,618, (1994); and Dietz et al., In Metal-Ion Separation and Preconcentration: Progress and Opportunities; Bond et al. Eds.; American Chemical Society: Washington, D.C., (1999); Vol. 716:234–250] and Pb2+ [Horwitz et al., Solvent Extr. Ion Exch. (1992), 10:313–336] analyses of terrestrial, aquatic, and bioassay samples.
The DtBuCH18C6 molecule can theoretically have 128 different isomeric designations; however, 20 diastereomers for each of the two t-butyl-substituted regioisomers (i.e., 4,4′ and 4,5′) result in only 40 symmetrically nondegenerate isomers. Due to differences in the conformation of the t-butylcyclohexano substituents (i.e., cis-syn-cis, cis-anti-cis, etc.), each of the different stereoisomers of DtBuCH18C6 can exhibit different cation complexation strengths. [Izatt et al., Chem. Rev. (1991) 91:1721–2085; Hay et al., RL3-6-C3-31; Pacific Northwest National Laboratory; Richland, Wash., (1996) and Hay, In Metal-Ion Separation and Preconcentration: Progress and Opportunities; Bond, et al. Eds.; American Chemical Society: Washington, D.C., (1999) Vol. 716:102–113.] Specifically, the cis/trans and cross-ring syn/anti conformational differences can effect diminished cation extraction arising from steric constraints imposed by the t-butylcyclohexano substituents, severely distorted oxygen donor arrays, and/or poor preorganization for cation complexation that requires a conformational rearrangement at a thermodynamic expense.
As a result of the application of DtBuCH18C6 in the removal of 90Sr from acidic nuclear wastes, as noted before, molecular modeling calculations have been performed to determine which of the 40 different isomers is the most efficient for the extraction of Sr2+ from HNO3. [Hay et al., RL3-6-C3-31; Pacific Northwest National Laboratory; Richland, Wash., (1996) and Hay, In Metal-Ion Separation and Preconcentration: Progress and Opportunities; Bond, et al. Eds.; American Chemical Society: Washington, D.C., (1999) Vol. 716:102–113.] Of the two isomers depicted in FIG. 1, molecular mechanics calculations have predicted that 4(z),4′(z)-cis-syn-cis-DtBuCH18C6 forms the most thermodynamically stable complexes with Sr2+, whereas 4(z),5′ (e)-cis-anti-cis-DtBuCH18C6 is predicted to form the least stable complexes.
The effects of conformational preorganization, which derive primarily from stereoisomerism rather than regioisomerism in this class of compounds, on the predicted distribution ratios for Sr2+ (DSr) are remarkable: DSr≈10 for 4(z),4′(z)-cis-syn-cis-DtBuCH18C6 and DSr≈0.022 for 4(z),5′(e)-cis-anti-cis-DtBuCH18C6 (0.1 M solutions in 1-octanol and 1 M HNO3). [Hay et al., RL3-6-C3-31; Pacific Northwest National Laboratory; Richland, Wash., (1996) and Hay, In Metal-Ion Separation and Preconcentration: Progress and Opportunities; Bond, et al. Eds.; American Chemical Society: Washington, D.C., (1999) Vol. 716:102–113.] These calculations clearly illustrate the significant impact that stereoisomeric effects can have on the efficiency of a given separation using dicyclohexano-18-crown-6 (DCH18C6)-based extractants and also point to the need for purification methods permitting the isolation or enrichment of those isomers having the most efficient Sr2+ extraction properties.
The catalytic hydrogenation of the di-t-butylbenzo-18-crown-6 (DtBuB18C6, FIG. 2) precursor of DtBuCH18C6 results in the formation of synthesis byproducts, the most frequently encountered of which are shown in FIG. 2. The catalytic hydrogenation of DtBuB18C6 can be presumed to occur in a step-wise manner to yield first 4-t-butylbenzo-4′(5′)-t-butylcyclohexano-18-crown-6 [(tBuB)(tBuCH)18C6] and finally DtBuCH18C6, which are depicted in the left column of FIG. 2. Depending on the hydrogenation conditions [Gula et al., U.S. Pat. No. 5,478,953 (1995)] and the activity of the heterogeneous rhodium (Rh) catalyst, ring cleavage reactions can produce a variety of acyclic molecules, and several possibilities are depicted in the right column of FIG. 2.
Continuing work on the purification of extractant molecules such as DtBuCH18C6 and the isolation of those stereoisomers predicted to be the most efficient Sr2+ extractants (i.e., 4(z),4′(z)-cis-syn-cis-DtBuCH18C6) has provided several strategies for the purification of predetermined extractants such as the stereoisomers of DtBuCH18C6 from the various aryl-containing under-hydrogenation products, ring cleavage products, and other inactive stereoisomers. The disclosure that follows describes two precipitation-based methods and a versatile method that utilizes solvent extraction third phase formation that can be used to purify impure samples and also to enrich the sample in the desired isomers; the latter method meeting several success criteria important to commercial application.